PATIENT INFORMATION LEAFLET

Patient Information Leaflet:Information for the User

Azacitidina Sandoz 25 mg/ml Powder for Injection EFG

Read this leaflet carefully before you start using this medicine,because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask yourdoctor,pharmacistor nurse.
• If you experience any side effects,consult your doctor, pharmacist or nurse,even if they are not listed in this leaflet. See section 4.

1.What is Azacitidina Sandoz and what it is used for

2.What you need to knowbeforestarting touseAzacitidina Sandoz

3.How to useAzacitidina Sandoz

4.Possible side effects

5Storage ofAzacitidina Sandoz

6.Contents of the pack and additional information

What is Azacitidina Sandoz

This medication is an anticancer agent that belongs to a group of medications called “antimetabolites”. This medication contains the active ingredient “azacitidina”.

What is Azacitidina Sandoz used for

Azacitidina is used in adults who cannot receive a stem cell transplant to treat:

• Malignant myelodysplastic syndromes (MDS) of higher risk.
• Chronic myelomonocytic leukemia (CMML).
• Acute myeloid leukemia (AML).

These diseases affect the bone marrow and can cause problems in the normal production of blood cells.

How Azacitidina Sandoz works

Azacitidina works by preventing the growth of cancer cells. Azacitidina incorporates into the genetic material of cells (ribonucleic acid [RNA] and deoxyribonucleic acid [DNA]). It is believed to act by altering the way cells activate or deactivate genes by interfering with the production of new RNA and DNA. It is believed that these actions correct the problems of maturation and growth of healthy blood cells in the bone marrow that cause myelodysplastic disorders, and that kill cancer cells in leukemia.

Consult a doctor or nurse if you have any questions about how azacitidina works or why you have been prescribed this medication.

Do not use Azacitidina Sandoz

• If you are allergic to azacitidina or any of the other components of this medication (listed in section 6).
• If you have advanced liver cancer.
• During lactation.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use azacitidina:

• If you have a decrease in platelet, red blood cell, or white blood cell count.
• If you have a kidney disease.
• If you have a liver disease.
• If you have ever had a heart disease or myocardial infarction, or have a history of lung disease.

Azacitidina may cause a severe immune reaction called “differentiation syndrome” (see section 4).

Blood tests

Before starting treatment with azacitidina and at the beginning of each treatment period (called “cycle”) blood tests will be performed. This is done to check that you have a sufficient number of blood cells and that your liver and kidneys are functioning correctly.

Children and adolescents

The use of azacitidina is not recommended in children and adolescents under 18 years old.

Other medications and Azacitidina Sandoz

Inform your doctor or pharmacist if you are using, have used recently, or may have to use any other medication. This is because azacitidina may affect the way other medications work. Similarly, other medications may affect the way azacitidina works.

Pregnancy,lactationand fertility

Pregnancy

You should not use azacitidina during pregnancy because it may be harmful to the baby.

If you are a woman and may become pregnant, you must use an effective contraceptive method while you are receiving azacitidina and for 6 months after completing treatment with azacitidina.

Inform your doctor immediately if you become pregnant during treatment.

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Lactation

Azacitidina should not be used during lactation. It is unknown whether this medication is excreted in breast milk.

Fertility

Males should not conceive a child while receiving treatment with azacitidina.

Males should use an effective contraceptive method while using azacitidina and for 3 months after completing treatment with azacitidina.

Consult your doctor if you wish to preserve your sperm before receiving this treatment.

Driving and operating machinery

Do not drive or use tools or machines if you experience adverse effects, such as fatigue.

Before administering azacitidina, your doctor will give you another medicine to prevent nausea and vomiting at the beginning of each treatment cycle.

• The recommended dose is 75 mg/m2of body surface area. Your doctor will decide your dose of this medicine based on your overall condition, height, and weight. Your doctor will monitor your progress and, if necessary, may change your dose.
• Azacitidina is administered every day for one week, followed by a three-week rest period. This “treatment cycle” will be repeated every four weeks. You will generally receive at least six treatment cycles.

A doctor or nurse will administer this medicine as a subcutaneous injection under the skin. It can be administered under the skin of the thigh, abdomen, or upper arm.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Inform your doctor immediately if you observe any of the following side effects:

• Drowsiness, tremors, jaundice, abdominal swelling, and bruising easily.They may be symptoms of liver failure and can be potentially fatal.
• Swelling of the legs and feet, back pain, decreased urine output, increased thirst, rapid pulse, dizziness, and nausea, vomiting, or decreased appetite and a feeling of confusion, restlessness, or fatigue.They may be symptoms of kidney failure and can be potentially fatal.
• Fever.It may be due to an infection as a result of having low white blood cell counts, which can be potentially fatal.
• Chest pain or difficulty breathing that may be accompanied by fever.It may be due to a lung infection known as "pneumonia" and can be potentially fatal.
• Bleeding.For example, blood in the stool due to bleeding in the stomach or intestine, or bleeding in the head. These may be symptoms of having low platelet counts in the blood.
• Difficulty breathing, swelling of the lips, itching, or skin rash.They may be due to an allergic reaction (hypersensitivity).

Other side effects include:

Frequent side effects(may affect more than 1 in 10 people)

• Decreased red blood cell count (anemia). You may feel tired and pale.
• Decreased white blood cell count. It may be accompanied by fever. You also have a higher probability of suffering from infections.
• Low platelet count in the blood (thrombocytopenia). You are more prone to bleeding and bruising.
• Constipation, diarrhea, nausea, vomiting.
• Pneumonia.
• Chest pain, difficulty breathing.
• Fatigue (fatigue).
• Reaction at the injection site, which includes redness, pain, or skin rash.
• Loss of appetite.
• Joint pain.
• Bruising.
• Skin rash.
• Red or purple spots under the skin.
• Abdominal pain.
• Itching.
• Fever.
• Sore throat and nasal congestion.
• Dizziness.
• Headache.
• Difficulty falling asleep (insomnia).
• Nasal bleeding (epistaxis).
• Muscle pain.
• Weakness (asthenia).
• Weight loss.
• Low potassium levels in the blood.

Frequent side effects(may affect up to 1 in 10 people)

• Bleeding in the head.
• Blood infection caused by bacteria (sepsis). It may be due to low white blood cell counts in the blood.
• Bone marrow failure. It may cause low red and white blood cell counts and platelet counts.
• A type of anemia in which there is a decrease in red and white blood cells and platelets.
• Urinary tract infection.
• A viral infection that causes herpes-like lesions.
• Bleeding from the gums, bleeding from the stomach or intestine, bleeding in the back due to hemorrhoidal bleeding, bleeding in the eyes, bleeding under the skin or inside the skin (hematoma).
• Blood in the urine.
• Mouth or tongue ulcers.
• Changes in the skin at the injection site. These may be swelling, a hard lump, bruising, bleeding into the skin (hematoma), skin rash, itching, and changes in skin color.
• Skin redness.
• Skin infection (cellulitis).
• Throat and nasal congestion, or sore throat.
• Nasal or sinus congestion.
• High or low blood pressure (hypertension or hypotension).
• Difficulty breathing when moving.
• Sore throat and larynx pain.
• Indigestion.
• Drowsiness (somnolence).
• Discomfort.
• Anxiety.
• Confusion.
• Hair loss.
• Kidney failure.
• Dehydration.
• A white coating on the tongue, the inside of the cheeks, and sometimes the palate, gums, and tonsils (fungal infection of the mouth).
• Fainting.
• Decreased blood pressure when standing (orthostatic hypotension) that causes dizziness when standing or sitting.
• Sleep, drowsiness (somnolence).
• Bleeding due to a catheter.
• A disease that affects the intestine and can cause fever, vomiting, and stomach pain (diverticulitis).
• Liquid around the lungs (pleural effusion).
• Tremors (chills).
• Muscle spasms.
• Rash with itching (urticaria).
• Liquid around the heart (pericardial effusion).

Rare side effects(may affect up to 1 in 1,000 people)

• Dry cough.
• Painless swelling of the fingertips (fingers like drumsticks).
• Tumor lysis syndrome – complications may occur during cancer treatment and sometimes even without treatment. These complications occur as a result of the product of dying cancer cells and may include: changes in blood biochemistry, high potassium, phosphorus, and uric acid levels, and low calcium levels that, therefore, generate changes in kidney function and heart rhythm, seizures, and sometimes death.

Unknown frequency(cannot be estimated from available data)

• Deep skin infection that spreads quickly damaging the skin and tissue, which can be potentially fatal (necrotizing fasciitis).
• Severe immune reaction (differentiation syndrome) that can cause fever, cough, difficulty breathing, skin rash, decreased urine output, low blood pressure (hypotension), swelling of the arms or legs, and rapid weight gain.
• Skin blood vessel inflammation that can cause skin rash (cutaneous vasculitis).

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSistema Español de Farmacovigilancia de medicamentos de Uso Humano:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Maintain this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the box and vial label after CAD/EXP. The expiration date is the last day of the month indicated.

Your doctor, pharmacist, or nurse is responsible for the conservation of azacitidina. They are also responsible for the correct preparation and disposal of unused medication.

For unopened vials of this medication:

This medication does not require special storage conditions.

If used immediately

The suspension must be administered within 60 minutes of preparation.

If used later

If azacitidina suspension is prepared using non-refrigerated injectable water, the suspension must be placed in the refrigerator (between 2 °C and 8 °C) immediately after preparation and must be stored in the refrigerator for a maximum of 24 hours.

If azacitidina suspension is prepared using injectable water that has been stored in the refrigerator (between 2 °C and 8 °C), the suspension must be placed in the refrigerator (between 2 °C and 8 °C) immediately after preparation and must be stored in the refrigerator for a maximum of 36 hours in the vial and up to 30 hours between 2 °C and 8 °C if stored in the syringe.

Allow the suspension to reach room temperature (between 20 °C and 25 °C) for up to 30 minutes before administration.

Do not use this medication if the suspension contains large particles.

Composition of Azacitidina Sandoz

• The active ingredient is azacitidina. A vial contains 100 mg of azacitidina. After reconstitution with 4 ml of water for injection, the reconstituted suspension contains 25 mg/ml of azacitidina.
• The other component is mannitol (E421).

Appearance of the product and contents of the package

Azacitidina Sandoz is a white powder for injectable suspension and is delivered in a glass vial with a rubber stopper and an aluminum seal with a plastic cap, containing 100 mg of azacitidina. The vial is stored in a cardboard box.

Package size: 1 vial.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Responsible for manufacturing

Pharmadox Healthcare Ltd,

KW20A Kordin Industrial Park

Paola, PLA3000

Malta

or

LEK farmacevtska družba d.d. (Lek Pharmaceuticals d.d.)

Verovškova ulica 57

1526 Ljubljana

Slovenia

or

Salutas Pharma GmbH

Otto-von-Guericke-Allee 1

Barleben, Sachsen-Anhalt, 39179

Germany

Last review date of thisleaflet:January 2024.

Thedetailed information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

Recommendations for safe handling

Azacitidina is a cytotoxic drug and, like other potentially toxic compounds, caution should be exercised when handling and preparing azacitidina suspensions. The procedures for correct handling and disposal of cancer medications should be applied.

If reconstituted azacitidina comes into contact with the skin, the area should be washed immediately and thoroughly with water and soap. If it comes into contact with mucous membranes, it should be washed thoroughly with water.

Incompatibilities

This medication should not be mixed with others, except as mentioned below (see "Reconstitution procedure").

Reconstitution procedure

Azacitidina Sandoz should be reconstituted with water for injection. The shelf life of the reconstituted medication can be extended by reconstituting it with refrigerated water for injection (between 2 °C and 8 °C). The following information is provided on the storage of the reconstituted medication.

1. The following items should be mounted:

Vial(s) of azacitidina; vial(s) of water for injection; non-sterile surgical gloves; alcohol-moistened wipes; syringe(s) for injection of 5 ml with needle(s).

1. 4 ml of water for injection should be withdrawn from the syringe, ensuring that the air trapped inside the syringe is purged.
2. The needle of the syringe containing the 4 ml of water for injection should be inserted through the rubber stopper of the vial of azacitidina; then, the water for injection should be injected into the vial.
3. After withdrawing the syringe and needle, the vial should be shaken vigorously until a uniform turbid suspension is obtained. After reconstitution, each ml of suspension will contain 25 mg of azacitidina (100 mg/4 ml). The reconstituted product is a turbid and homogeneous suspension, without aggregates.The product should be discarded if it contains large particles or aggregates. Do not filter the suspension after reconstitution, as this may eliminate the active ingredient. It should be noted that some adapters, infusion needles, and closed systems contain filters; therefore, these systems should not be used for administering the medication after reconstitution.
4. The rubber stopper should be cleaned and a new syringe with a needle should be inserted into the vial. Then, the vial should be inverted, ensuring that the tip of the needle is below the liquid level. Next, the plunger should be pulled back to withdraw the amount of medication needed for the correct dose, ensuring that the air trapped inside the syringe is purged. Then, the syringe with the needle should be withdrawn from the vial and the needle should be discarded.
5. Next, a new subcutaneous needle (it is recommended to use a caliber 25) should be tightly attached to the syringe. The needle should not be purged before injection, in order to reduce the incidence of local reactions at the injection site.
6. If more than 1 vial is needed, all the above steps should be repeated for the preparation of the suspension. In the case of doses that require more than 1 vial, the dose should be divided into equal parts, for example, a dose of 150 mg = 6 ml; two syringes with 3 ml in each syringe. Due to retention in the vial and the needle, it may not be possible to withdraw all the suspension from the vial.
7. The contents of the dosing syringe should be resuspended immediately before administration. The syringe with the reconstituted suspension should be allowed to reach an ambient temperature of approximately between 20 °C and 25 °C for 30 minutes before administration. If the time elapsed is greater than 30 minutes, the suspension should be discarded properly and a new dose should be prepared. To resuspend, vigorously roll the syringe between the palms of the hands until a uniform and turbid suspension is obtained.The product should be discarded if it contains large particles or aggregates.

Storage of the reconstituted medication

When azacitidina is reconstituted using water for injection that has not been refrigerated, the chemical and physical stability in use of the reconstituted medication has been demonstrated at 25 °C for 60 minutes and between 2 °C and 8 °C for 24 hours stored in the vial and in the syringe.

The shelf life of the reconstituted medication can be extended by reconstituting it with refrigerated water for injection (between 2 °C and 8 °C). When azacitidina is reconstituted using refrigerated water for injection (between 2 °C and 8 °C), the chemical and physical stability in use of the reconstituted medication has been demonstrated between 2 °C and 8 °C for 36 hours stored in the vial and for 30 hours between 2 °C and 8 °C if stored in the syringe.

From a microbiological point of view, the reconstituted product should be used immediately. If not used immediately, the times and conditions of storage in use before use are the responsibility of the user and should not exceed 24 hours between 2 °C and 8 °C.

Calculation of an individual dose

The total dose, according to the body surface area (SC), can be calculated as follows:

Total dose (mg) = dose (mg/m2) × SC (m2)

The following table is only an example of how to calculate individual doses of azacitidina based on an average SC value of 1.8 m2.

Administration form

Do not filter the suspension after reconstitution.

Azacitidina Sandoz reconstituted should be injected subcutaneously (insert the needle at an angle of 45 to 90°) with a caliber 25 needle in the upper arm, thigh, or abdomen.

Doses greater than 4 ml should be injected in two separate locations.

The injection sites should be rotated. New injections should be administered at least 2.5 cm away from the previous site and never in sensitive areas, with hematomas, redness, or hardening.

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.